Modified .alpha.-D-Glc.rho.-(1-2)-.alpha.-D-Glc.rho.-(1-3)-.alpha.-D-Glc.rho.-ana logues
Disclosed is the trisaccharide .alpha.-D-Glcp-(1-2)-.alpha.-D-Glcp-(1-3)-.alpha.-D-Glcp and compounds related thereto as well as pharmaceutical compositions thereof.
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Claims
1. A compound useful in the synthesis of modified trisaccharide.alpha.-glucosidase I inhibitors represented by Formula I: ##STR5## wherein each Y is independently selected from the group consisting of --O-- and NH, R is an aglycon of from 1 to 20 carbon atoms, R.sup.1 is selected from the group consisting of --CH.sub.2 CH.dbd.CH.sub.2 and hydrogen, and R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are protecting groups capable of being differentially removed as compared to --O--CH.sub.2 CH.dbd.CH.sub.2.
2. The compound of claim 1 wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are benzyl and R.sup.1 is hydrogen.
3. The compound of according to claim 2 wherein each Y is --O--.
4. A compound useful in the synthesis of modified trisaccharide.alpha.-glucosidase I inhibitors represented by Formula II: ##STR6## wherein each Y is independently selected from the group consisting of --O-- and --NH--, R is an aglycon of from 1 to 20 carbon atoms, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are protecting groups, R.sup.6 and R.sup.7 are independently selected from the group consisting of --O--Pr, hydrogen, fluoro, azido, and --OCH.sub.3 where Pr is a protecting group, R.sup.8 is selected from the group consisting of --CH.sub.2 --O--Pr, CH.sup.2 --OH, --CH.sub.2 --H, --CH.sub.2 --fluoro, --CH.sub.2 -azido and --CH.sub.2 --OCH.sub.3 where Pr is a protecting group, and R.sup.9 is selected from the group consisting of hydrogen and a protecting group.
5. The compound of claim 4 wherein R.sup.6, R.sup.7 and R.sup.8 are selected as set forth below:
6. A compound represented by Formula III: ##STR7## wherein each Y is independently selected from the group consisting of O and NH and X is selected from the group consisting of xylose, valienamine, validamine, valiolamine, 5-deoxy-5-thioglucose, homonorijimycin, 1,5-trans-(C)-glucopyranosylamine and a compound of the formula: ##STR8## wherein R.sup.6 and R.sup.7 are independently selected from the group consisting of --O--Pr, hydrogen, fluoro, azido, and --OCH.sub.3 where Pr is a protecting group, R.sup.8 is selected from the group consisting of --CH.sub.2 --O--Pr, --CH.sub.2 --H, --CH.sub.2 --fluoro, --CH.sub.2 -azido and --CH.sub.2 --OCH.sub.3 where Pr is a protecting group, W is selected from the group consisting of hydrogen, hydroxyl, alkoxy of from 1 to 4 carbon atoms, fluoro, chloro, and amino; and R is an aglycon of from 1 to 20 carbon atoms and which compounds inhibit the glucosidase activity.
7. A pharmaceutical composition comprising a pharmaceutically inert carrier and from 0.1 to 95 weight percent of a compound according to claim 5.
8. The compound of claim 6 wherein R is --(CH.sub.2).sub.8 COOCH.sub.3 and W is --OH and X is a compound of the formula: ##STR9##
9. The compound of claim 8 wherein each Y is oxygen.
10. The compound of claim 9 wherein R.sup.6 is hydrogen, R.sup.7 is hydroxyl and R.sup.8 is hydroxyl.
11. The compound of claim 9 wherein R.sup.6 is methoxy, R.sup.7 is hydroxyl and R.sup.8 is hydroxyl.
12. The compound of claim 9 wherein R.sup.6 is hydroxyl, R.sup.7 is hydrogen and R.sup.8 is hydroxyl.
13. The compound of claim 9 wherein R.sup.6 is hydroxyl, R.sup.7 is methoxy and R.sup.8 is hydroxyl.
14. The compound of claim 9 wherein R is hydroxyl, R is hydroxyl and R is methyl.
| 0 173 948 | March 1986 | EPX |
| 0 422 975 | April 1991 | EPX |
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Type: Grant
Filed: Jun 7, 1995
Date of Patent: Jul 27, 1999
Assignee: Alberta Research Council (Edmonton)
Inventors: Om Srivastava (Edmonton), Roman Szweda (Edmonton)
Primary Examiner: Elli Peselev
Law Firm: Burns, Doane, Swecker & Mathis, L.L.P.
Application Number: 8/485,057
International Classification: A61K 3170; C07H 1500;
